Data extraction

Main results

6 trials met the inclusion criteria and had data suitable for analysis. 6 trials evaluated
CIBIC-plus. At 6 months, galantamine in doses of 16, 24, and 32 mg/d showed improvements
(Table), but a dose of 8 mg/d did not. All 3 trials evaluating ADAS-cog showed improvements
of ≥ 4 points at 6 months with galantamine in doses of 16, 24, and 32 mg/d (Table)
but not with a dose of 8 mg/d. 1 trial each evaluated ADCS-ADL and NPI scores: Each
showed improvements with galantamine, 16 and 24 mg/d, but not with 8 mg/d. 1 trial
evaluated DAD scores: Galantamine, 32 mg/d, but not 24 mg/d showed improvements. Galantamine,
at least in higher doses, increased the frequency of adverse events, including tremor,
anorexia, vomiting, nausea, weight loss, headache, abdominal pain, diarrhea, dizziness,
and agitation. More patients receiving galantamine stopped taking their medication
because of adverse events.

Conclusion

In patients with suspected Alzheimer disease, galantamine, in doses between 16 and
32 mg/d, improves global clinical status, cognition, activities of daily living, and
behavior but also causes more adverse events than does placebo.

Commentary

The meta-analysis by Olin and Schneider shows that galantamine has efficacy similar
to tacrine, donepezil, and rivastigmine, the 3 acetylcholinesterase inhibitors (AChE-Is)
currently marketed in the United States for treatment of AD. Their comparable efficacy
suggests that touted unique properties, such as the allosteric modulation of nicotinic
receptors with galantamine, may not confer a measurable added benefit; however, head-to-head
trials of galantamine and its competitors are needed to definitively determine this.
In the meantime, clinicians should continue to select an AChE-I on the basis of adverse-effect
profile, patient tolerance, convenience of dosing, and cost. Although anecdotal reports
show clinical improvement after switching nonresponders to a different AChE-I, no
published data support this practice.

The functional dependence, behavioral disturbances, and memory loss that are part
of Alzheimer disease contribute to institutionalization and caregiver stress. Because
of the uncertain clinical relevance of the ADAS-cog, recent clinical trials of AD
treatments have incorporated instruments to assess their effect on activities of daily
living and behavioral complications (1, 2). The slowing of decline in activities of daily living by galantamine and other AChE-Is,
as well as these agents' potential to mitigate behavioral disturbances, are important
reasons to recommend AChE-Is for patients with AD. Although the major clinical trials
have not included patients with advanced AD, long-term, open-label studies suggest
that AChE-Is may delay institutionalization (3).